Patients Treated for SCID (1968-2010)

This study is currently recruiting participants.
Verified January 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01346150
First received: April 29, 2011
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

People with Primary Immune Deficiency (PID) may develop severe, life-threatening infections as a result of inherited defects in the genes that normally instruct blood-forming cells to develop and to fight infections. PID diseases include Severe Combined Immune Deficiency (SCID), leaky SCID, Omenn syndrome (OS), and Reticular Dysgenesis (RD). PIDs may be treated by transplantation of bone marrow stem cells from a healthy person or, in some cases, by enzyme replacement or by gene therapy. Patients with SCID were among the first to receive bone marrow stem cell (also called hematopoietic cells) transplantation (HCT) more than 40 years ago, and HCT is the standard treatment today for this group of diseases. Since PID diseases are rare, there are not enough patients at any single center to determine the full range of causes, natural history, or best methods of treatment. For this research study many PID centers across North America have organized into the Primary Immune Deficiency Treatment Consortium (PIDTC) to pool their experience and study PIDs together. Researchers will collect information on your general health, psychological and developmental health, and the current status of your immune system to help better define future approaches to PID treatments.


Condition
SCID
ADA-SCID
XSCID
Leaky SCID
Omenn Syndrome
Reticular Dysgenesis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: A Retrospective and Cross-Sectional Analysis of Patients Treated for SCID (1968-2010) (RDCRN PIDTC-6902)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Retrospective Study - Part 1 [ Time Frame: 1, 5, 10, 20, >20 years ] [ Designated as safety issue: No ]
    Overall survival

  • Cross-Sectional Study - Part 2 [ Time Frame: 2 to > 20 years ] [ Designated as safety issue: No ]
    Full immune reconstitution


Secondary Outcome Measures:
  • Retrospective Study Part 1 [ Time Frame: 1 year to > 20 years ] [ Designated as safety issue: No ]
    Immune reconstitution and clinical outcomes

  • Retrospective Study - Part 1 [ Time Frame: 3 months to >20 years ] [ Designated as safety issue: No ]
    Engraftment

  • Cross-Sectional Study - Part 2 [ Time Frame: 2 to >20 years ] [ Designated as safety issue: No ]
    Current state of lineage-specific chimerism

  • Cross-Sectional Study - Part 2 [ Time Frame: 2 to >20 years ] [ Designated as safety issue: No ]
    Current status of health


Biospecimen Retention:   Samples With DNA

Biospecimens may include blood, other tissues (e.g., buccal swab or brushing, hair follicles), and/or bone marrow.


Estimated Enrollment: 1146
Study Start Date: May 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Stratum A
SCID, ADA-SCID, and XSCID who received a transplant
Stratum B
Leaky SCID, Omenn Syndrome, and Reticular Dysgenesis who received a transplant
Stratum C
SCID who received PEG ADA or gene therapy

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with diagnosis of SCID or SCID variants treated at Consortium Centers from 1968-2010

Criteria

Investigators from institutions participating in this consortium will submit data to the PIDTC Review Panel to determine eligibility and stratum assignment. The eligibility of the patients and their stratification by SCID variant and treatment employed for SCID will be as follows.

Inclusion Criteria:

Strata A, B, and C (Part 1 - Retrospective Study).

Patients eligible for the retrospective analysis include all patients diagnosed to have SCID who were treated at the institutions participating in this consortium from 1968 until December 31, 2010, who are not already enrolled on PIDTC Protocol 1. Subjects who received HCT/GT/ERT prior to December 31, 2010 are eligible for the retrospective study. The enrollment criteria for subjects who died prior to definitive therapy are the same as for Strata A, B and C.

Stratum A, Typical SCID. Patients who meet the following inclusion criteria and who received HCT are eligible for enrollment into Stratum A (Classic SCID) of the study: Absence or very low number of T cells (CD3 T cells < 300/microliter), and no or very low T cell function (< 10% of lower limit of normal) as measured by response to phytohemagglutinin (PHA) or T cells of maternal origin present, but with < 10% of normal T cell function (as measured by response to PHA).

Stratum B, Leaky SCID, Omenn Syndrome, Reticular Dysgenesis. Patients who meet the following criteria are eligible for enrollment into Stratum B of the study: Leaky SCID

  • Reduced number of CD3 T cells - for age up to 2 years ≥ 300 and < 1000/microliter; for > 2 years up to 4 years ≥ 300 and < 800/microliter ; for > 4 years ≥ 300 and < 600/microliter
  • Absence of maternal engraftment ≥ 10% and ≤ 30% of lower limit of normal T cell function (as measured by response to PHA)

Omenn Syndrome (OS)

  • Generalized skin rash
  • Absence of maternal engraftment
  • Detectable CD3 T cells, ≥ 300/microliter
  • Absent or low (up to 30% of normal) T cell proliferation to antigens to which the patient has been exposed
  • If the proliferation to antigen was not performed, but at least 4 of the following 9 supportive criteria, at least one of which must be among those marked with an asterisk (*) are present, the patient is eligible: Hepatomegaly; Splenomegaly; Lymphadenopathy; Elevated IgE; Elevated absolute eosinophil count; *Oligoclonal T cells measured by CDR3 length or flow cytometry >80% of CD4+ T cells are CD45RO+ ; *Proliferation to PHA is reduced <30% of lower limit of normal or SI <20; *Proliferative response in mixed leukocyte reaction is reduced <30% of lower limit of normal or SI <5

Reticular Dysgenesis (RD)

  • Absence or very low number of T cells (CD3 T cells <300/microliter)
  • No or very low (<10% of lower limit of normal) T cell function (as measured by response to phytohemagglutinin (PHA)
  • Severe congenital neutropenia (absolute neutrophil count <200/microliter)
  • Sensorineural deafness and/or absence of granulopoiesis at bone marrow examination

Stratum C, SCID with Non-HCT Treatments. Patients who meet the following criteria and were treated with PEG-ADA or gene therapy with autologous modified cells are eligible for enrollment into Stratum C (SCID with non-HCT treatments) of the study.

  • ADA Deficient SCID treated with PEG-ADA
  • Any SCID treated with gene therapy

Strata A, B, and C (Part 2 - Cross-Sectional Study)

Patient inclusion criteria for the cross sectional study: Eligibility for Strata A, B and C are the same as for the retrospective study except that all the patients in the cross-sectional study are currently surviving and are at least 2 years post the most recent class of therapy.

Exclusion Criteria:

Parts 1 and 2 - Retrospective and Cross-Sectional Studies

  • Lack of appropriate testing to rule out HIV infection after 1997 (p24 antigen or more sensitive) or other cause of secondary immunodeficiency
  • Presence of DiGeorge syndrome
  • Most patients with other PIDs such as nucleoside phosphorylase deficiency, ZAP70 deficiency, CD40 ligand deficiency, NEMO deficiency, XLP, cartilage hair hypoplasia or ataxia telangiectasia will not meet the inclusion criteria for Stratum A, B, or C above. However, a patient with one of the above may meet the inclusion criteria for Stratum B and if so will be included.
  • MHC Class I and MHC Class II antigen deficiency are excluded
  • Metabolic conditions that imitate SCID or related disorders such as folate transporter deficiency, severe zinc deficiency, transcobalamin deficiency
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01346150

  Show 33 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Richard J O'Reilly, MD Memorial Sloan-Kettering Cancer Center
Principal Investigator: Morton J Cowan, MD UCSF Children's Hospital
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01346150     History of Changes
Other Study ID Numbers: DAIT RDCRN PIDTC-6902
Study First Received: April 29, 2011
Last Updated: January 27, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Congenital Abnormalities
Severe Combined Immunodeficiency
Leukopenia
X-Linked Combined Immunodeficiency Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Leukocyte Disorders
Hematologic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on April 23, 2014